Clinical Question: Is efalizumab effective in the treatment of plaque psoriasis?
Setting: Outpatient (specialty)
Study Design: Randomized controlled trial (double-blinded)
Synopsis: In the first stage of this study, patients older than 18 years with moderate to severe, but stable plaque psoriasis covering at least 10 percent of their body were assigned randomly (unclear if allocation was concealed) to receive placebo (n = 122) or subcutaneous injections of efalizumab (232 patients received 1 mg per kg per week, and 243 received 2 mg per kg per week). To maintain the blinding, the researchers used different volumes of placebo to match the dosages of the study drug.
In the second stage, after 12 weeks, patients who had received active treatment were stratified into three subgroups based on the level of improvement from baseline. The two subgroups who demonstrated at least a 50 percent improvement were randomized once more to receive placebo, efalizumab in a dosage of 2 mg per kg per week, or efalizumab in a dosage of 2 mg per kg every other week. Those patients who demonstrated less than 50 percent response were randomized again to receive placebo or efalizumab in a dosage of 4 mg per kg per week.
The total duration of follow-up was 36 weeks. The only outcome used in this study was a clinician-assessed psoriasis index determined by its extent and severity, assessed by intention to treat. The range of values for this index is zero to 72, with higher scores representing greater severity. All patients, evaluators, and data analysts were unaware of treatment assignment.
At the end of 12 weeks, only 5 percent of patients taking placebo experienced at least 75 percent improvement in the psoriasis index, compared with 22 percent of patients taking the lower dosage of efalizumab and 28 percent taking the higher dosage (number needed to treat = six and four, respectively). Unfortunately, the authors do not report the absolute differences in scores, so it is unclear if the relative improvement is clinically meaningful. For the second stage of the study, the patients with stronger responses did equally well on either dosage and, not surprisingly, did worse on placebo. Higher dosages of efalizumab were more effective in patients who had minimal to moderate responses during the first treatment period. The total dropout rate was similar for each group.
Bottom Line: In patients with moderate to severe plaque psoriasis, efalizumab injections improve clinician-assessed severity by 12 weeks. Longer therapy improves outcomes even more but requires dosing tailored to the initial response. Whether this was beneficial from the patients’ perspective is unclear. (Level of Evidence: 1b)